7-141928139-T-C

Variant names:

• chr7-141928139-T-C
• rs1285935
• NM_013252.3:c.*1965A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013252.3(CLEC5A):​c.*1965A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,120 control chromosomes in the GnomAD database, including 55,982 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.86 (55940 hom., cov: 29)
  • Exomes 𝑓: 0.89 (42 hom.)
• Consequence: CLEC5A NM_013252.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 7 publications found

Genes affected

CLEC5A (HGNC:2054): (C-type lectin domain containing 5A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type II transmembrane protein interacts with dnax-activation protein 12 and may play a role in cell activation. Alternative splice variants have been described but their full-length sequence has not been determined. [provided by RefSeq, Jul 2008]

MGAM (HGNC:7043): (maltase-glucoamylase) This gene encodes maltase-glucoamylase, which is a brush border membrane enzyme that plays a role in the final steps of digestion of starch. The protein has two catalytic sites identical to those of sucrase-isomaltase, but the proteins are only 59% homologous. Both are members of glycosyl hydrolase family 31, which has a variety of substrate specificities. [provided by RefSeq, Jul 2008]

MGAM Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC5A	NM_013252.3	c.*1965A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000546910.6	NP_037384.1
CLEC5A	XR_007059995.1	n.1903A>G		non_coding_transcript_exon_variant	Exon 8 of 8
CLEC5A	NM_001301167.2	c.*1965A>G		3_prime_UTR_variant	Exon 6 of 6		NP_001288096.1
CLEC5A	XM_011515995.3	c.*1965A>G		3_prime_UTR_variant	Exon 5 of 5		XP_011514297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC5A	ENST00000546910.6	c.*1965A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_013252.3	ENSP00000449999.1
MGAM	ENST00000465654.5	c.-179-17682T>C		intron_variant	Intron 1 of 5	3		ENSP00000419372.1
MGAM	ENST00000497554.1	n.37-1638T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130131 AN: 151898 Hom.: 55892 Cov.: 29

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.840

GnomAD4 exome AF: 0.894 AC: 93 AN: 104 Hom.: 42 Cov.: 0 AF XY: 0.857 AC XY: 60 AN XY: 70

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.885 AC: 85 AN: 96

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 6 AN: 6

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.857 AC: 130238 AN: 152016 Hom.: 55940 Cov.: 29 AF XY: 0.855 AC XY: 63545 AN XY: 74294

African (AFR) AF: 0.914 AC: 37901 AN: 41456

American (AMR) AF: 0.859 AC: 13116 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3026 AN: 3468

East Asian (EAS) AF: 0.738 AC: 3799 AN: 5148

South Asian (SAS) AF: 0.834 AC: 4022 AN: 4820

European-Finnish (FIN) AF: 0.844 AC: 8922 AN: 10566

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.833 AC: 56623 AN: 67980

Other (OTH) AF: 0.839 AC: 1766 AN: 2106

Alfa AF: 0.846 Hom.: 34716

Bravo AF: 0.858

Asia WGS AF: 0.793 AC: 2756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.86
DANN	Benign	0.48
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1285935; hg19: chr7-141627939; COSMIC: COSV69398050; COSMIC: COSV69398050;